Journal article
PSD95: A synaptic protein implicated in schizophrenia or autism?
Progress in neuro-psychopharmacology & biological psychiatry, v 82, pp 187-194
02 Mar 2018
PMID: 29169997
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-d-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism. For instance, recent genomic and sequencing studies of psychiatric patients highlight the aberrations at the PSD of glutamatergic synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency shows alterations in NMDA and AMPA-receptor composition and function in specific brain regions that may contribute to phenotypes observed in neuropsychiatric pathologies. In this review, we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment. More specifically, we discuss its interactions with NMDA receptor subunits that potentially affect glutamate transmission, and the formation of silent synapses during critical time points of neurodevelopment. Furthermore, we describe how PSD-95 may alter dendritic spine morphologies, thus regulating synaptic function that influences behavioral phenotypes in SCZ versus autism. Understanding the role of PSD-95 in the neuropathologies of SCZ and autism will give an insight of the cellular and molecular attributes in the disorders, thus providing treatment options in patients affected.
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Details
- Title
- PSD95: A synaptic protein implicated in schizophrenia or autism?
- Creators
- Austin A Coley - Drexel UniversityWen-Jun Gao - Drexel University
- Publication Details
- Progress in neuro-psychopharmacology & biological psychiatry, v 82, pp 187-194
- Publisher
- Elsevier
- Grant note
- K00 MH124182 / NIMH NIH HHS F99 NS105185 / NINDS NIH HHS R01 MH085666 / NIMH NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000424701600017
- Scopus ID
- 2-s2.0-85034808799
- Other Identifier
- 991019167639804721
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Highly Cited Paper
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry